Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse brain invasion is a major reason for poor prognosis of glioma patients. The molecular mechanisms underlying infiltration are different from those of other cancer types. To detect genes associated with glioma invasion, highly migratory clones were selected from U373MG glioma cells and from primary glioblastoma cells, and the gene expression pattern of these "fast" cells was compared with that of the original ("slow") cells using oligonucleotide microarrays comprising 12,625 genes. A total of 28 genes were differently expressed in both primary and established cell populations, including 19 genes that were upregulated and 9 that were downregulated in fast cells. Most of these genes have not been linked to glioma invasion so far. Specifically, differentially expressed genes included those encoding extracellular matrix components (COL16A1, DPT), proteases (CATD, PRSS11), cytokines (MDK, IL8), transport proteins (SLC1A3, ATP10B), cytoskeleton constituents (ACTA2, ACTSG, NEFL), DNA repair enzymes (WRN, ADPRTL2), and G-protein signaling components (GNA12, RGS3, RGS4). RGS3 and RGS4, which are homologs of the Drosophila glia gene loco, were further functionally analyzed. U373MG glioma cell clones overexpressing RGS3 or RGS4 showed an increase of both adhesion and migration. These findings expand the spectrum of possible molecular pathways underlying the invasion of neoplastic astrocytes. Specifically, they suggest that RGS proteins and G-protein-mediated signal transduction are evolutionary conserved functional players.
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PMID:Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility. 1505 45

The Werner syndrome (WS) protein (WRN), a DNA helicase/exonuclease, is required for genomic stability and avoidance of cancer. Current evidence suggests that WRN is involved in the resolution of stalled and/or collapsed replication forks. This function is indicated, in part, by replication defects in WS cells and by hypersensitivity to agents causing major structural aberrations in DNA that block replication. We show here that antisense suppression of WRN in two human glioma cell lines reproduces hallmarks of the drug cytotoxicity profile of WS cells, namely, hypersensitivity to 4-nitroquinoline 1-oxide, camptothecin and hydroxyurea. We also show that antisense-treated cells are hypersensitive to methyl-lexitropsin, a site-specific alkylating agent that produces mainly N3-methyladenine, a cytotoxic and replication-blocking lesion. Antisense-treated cells are hypersensitive to O(6)-methylguanine adducts as well, but only when repair by O(6)-methylguanine-DNA methyltransferase is lacking. Our results illustrate the drug sensitivity caused by deficiency of WRN in a uniform genetic background. They extend the WRN DNA damage sensitivity spectrum to methyl base adducts that can result in blocked replication, and suggest that WRN may be required for resumption of processive replication when incomplete repair of DNA damage leaves blocking lesions at forks. The evidence that highly disparate lesions fall within the purview of WRN, and that abrogating DNA repair can reveal dependence on WRN, suggests that WRN may protect the genome from the lethal, mutagenic and carcinogenic effects of widely diverse DNA damage arising from endogenous processes and environmental agents.
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PMID:The Werner syndrome protein confers resistance to the DNA lesions N3-methyladenine and O6-methylguanine: implications for WRN function. 1513 30

Werner syndrome (WS) is a premature aging disorder characterized by early onset of symptoms related to normal aging and by a high predisposition to various types of cancer, including gliomas. WS is caused by inherited recessive mutations in the WRN gene, which encodes a helicase considered a caretaker of the genome. Aiming to study the role of WRN Cys1367Arg in glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of this single nucleotide polymorphism in 94 glioma patients and 100 healthy subjects. Comparisons of genotype distributions and allele frequencies did not reveal any significant difference between the groups. Overall and disease-free survival rates were calculated, but no statistically significant difference was observed. Our data suggest that WRN Cys1367Arg SNP is not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.
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PMID:WRN Cys1367Arg SNP is not associated with risk and prognosis of gliomas in Southeast Brazil. 1867 Jul 36

Tumor segmentation is of great importance for diagnosis and prognosis of brain cancer in medical field. Because of the noise, inhomogeneous gray, diversity of tissue, bias among modalities, and the fuzzy boundaries between tumor and adjacent tissues in the magnetic resonance imaging (MRI), tumor segmentation is a very difficult task. At present, many of the existing brain tumor segmentation methods are semi-automatic which are troublesome and inconvenient because interventions of raters or specialists are required. In this paper an automatic method, named wide residual network & pyramid pool network (WRN-PPNet), which can automatically segment glioma end to end is put forward. The main idea is described below. Firstly, WRN is used to extract features of multimodal brain tumor slices which are proved to have strong expressive ability. Secondly, the global prior representation with different level obtained by PPNet is stacked on the features from WRN. Finally, the scale recovery module in which the original inputs are fed into the network again is utilized to produce the pixel-level predictions which have the same size with the original inputs. Dice coefficients, sensitivity coefficient and predictive positivity value (PPV) coefficient are used to evaluate the performance of WRN-PPNet quantitatively. The experimental results show that the proposed method has a superior performance compared with the other state-of-the-art methods, and the average Dice, sensitivity and PPV on the randomly selected test data can reach 0.91, 0.94 and 0.89 respectively.
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PMID:Multimodal brain tumor image segmentation using WRN-PPNet. 3115 88